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Serine Hydroxymethyltransferase 1 (SHMT1) is an enzyme which is encoded by the SHMT1 gene, forming part of the one carbon pathway, which is in turn part of the greater “methylation cycle”. Dietary folate or folic acid is converted into tetrahydrafolate (THF), which forms the entry point into the one carbon cycle 1.

SHMT1 converts THF and the amino acid serine into 5,10-methylenetetrahydrofolate (MeTHF) and the amino acid glycine. MeTHF is the molecule that the enzyme methylene tetrahydrofolate reductase (MTHFR) breaks down into 5-methlytetrahydrofolate (MTHF). The MTHFR reaction is often the limiting step of the one carbon pathway, with several polymorphisms in MTHFR associated with poor health outcomes. Therefore, ensuring an adequate supply of MeTHF (which is the function of SHMT1) for MTHFR to breakdown is key to minimizing its impact 2,3.

MeTHF is also required for the formation of new DNA and RNA, promoting healthy cell division which is especially important in the immune system.

There is one SNP in SHMT1 , rs1979277, which has been associated with poor health outcomes.


Science Grade
Heart Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1979277 c t 37 Leu Phe

Risk Description

The risk allele ‘T’ of C1420T in the SHMT gene was associated with an increased cardiovascular risk when associated with the risk ‘T’ allele of C667T (rs1801133) in the MTHFR gene 4.

The ‘T’ allele of C1420T is associated with an alteration in SHMT enzyme localisation within the cell, which in turn reduces the availability of MeTHF, the substrate which is required by the MTHFR enzyme 5. This reduction in MeTHF availability coupled with the reduced MTHFR enzyme activity associated with the risk ‘T’ allele of C667T in the MTHFR gene 6 leads to a significant increase in cardiovascular risk, thought to be driven by homocysteine accumulation.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin B6 Pyridoxal phosphate

Vitamin B6 is a cofactor for SHMT which converts THF to MeTHF which is in turn converted into MTHF by the enzyme MTHFR. Vitamin B6 binds with SHMT and allows it to function optimally, when present in low levels SHMT activity is reduced 7.

Although the risk allele ‘T’ of C1420T is not associated with reduced activity it is associated with a reduced availability of MeTHF, which limits MTHFR activity. Therefore, supplementation may prove beneficial by maximising SHMT activity, leading to a proper supply of MeTHF.

Additionally, two enzymes are required to convert harmful homocysteine into the amino acid cysteine: cystathionine β synthase (CBS) and cystathionine γ ligase CTH). Both of these enzymes also use vitamin B6 as a cofactor, and so vitamin B6 supplementation may additionally benefit their activity, reducing the pool of homocysteine 8.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Folate Methyltetrahydrofolate

Proper folate intake is associated with numerous health benefits, especially for infants or during pregnancy. Therefore, many western foods, particularly cereals, are fortified with folic acid.

However, an excess of folic acid, is associated with an increased risk of developing certain cancers. To avoid this effect, rather than supplementing with folic acid which can accumulate, due to a lack of processing through MTHFR, leading to adverse health effects, MeTHF may be used instead to bypass this effect 9.

MeTHF is the produced by SHMT and its availability is reduced in those carrying the risk ‘T’ allele of C1420T. MeTHF supplementation may be beneficial by bypassing this limitation, providing adequate substrate for MTHFR.

Discuss this information with your doctor before taking any course of action.


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